Pembrolizumab reduced the risk for recurrence of stage 3 melanoma
A one-year course of 18 doses of pembrolizumab significantly reduced the risk of recurrence for patients with stage 3 melanoma who were at high risk of recurrence after surgery, according to data from the KEYNOTE-054/EORTC 1325-MG phase III clinical trial. These results were presented by Alexander M.M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, on Sunday at the AACR Annual Meeting 2018.
Eggermont and colleagues enrolled 1,019 patients with stage 3 melanoma who were at high risk of recurrence after complete resection of their tumors in the KEYNOTE-054/EORTC 1325-MG phase III clinical trial. Patients were randomized 1:1 to a flat dose of 200 milligrams of pembrolizumab or placebo every three weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity.
After a median follow-up of 1.25 years, 135 of the 514 patients randomized to pembrolizumab and 216 of the 505 patients randomized to placebo had been diagnosed with recurrent disease or had died.
For all the patients randomized to pembrolizumab, the 12-month recurrence-free survival rate was 75.4 percent, compared with 61.0 percent for all those randomized to placebo (HR 0.57, 98,4% CI 0.43-0.74: p < 0,0001). Thus, overall, patients randomized to pembrolizumab were 43 percent less likely to have recurrence.
The benefits of pembrolizumab were similar when patients with PD-L1-positive and PD-L1- negative tumors were analyzed separately. Among the 852 patients with PD-L1-positive tumors, those randomized to pembrolizumab were 46 percent less likely to have a recurrence or death event compared with those randomized to placebo (Hr 0.54, 95% CI 0.42-0.69; p < 0.0001). Among the 116 patients with PD-L1-negative tumors, those randomized to pembrolizumab were 53 percent less likely to have a recurrence or death event (HR 0.47, 95% CI 0.47 [0.26, 0.85]; p = 0.01).
Drug-related grade 3 to 5 adverse events were reported in 14.7% (n = 75) in the pembrolizumab group and 3.4% (n = 17) in the placebo group. There was only one pembrolizumab-related death due to myositis. The highest incidence of immune-related adverse events (irAEs), mostly grade 1 to 2, observed in the pembrolizumab vs placebo group were endocrine disorders (23.4% versus 5.0%). The incidence of grade 3-4 irAEs was 7.1% vs 0.6%: colitis (2.0% vs 0.2%), pneumonitis (0.8% vs 0%), hepatitis (1.4% vs 0.2%), all others had incidences < 1%
We hope that these data will lead to regulators in the United States and Europe approving pembrolizumab as a new treatment option for these patients”, said Eggermont.
»An important aspect of this trial is that patients randomized to placebo who have recurrence are offered access to Pembrolizumab. This cross-over design is unique in the world of adjuvant trials in melanoma and will permit us to analyze if adjuvant therapy with pembrolizumab right after surgery is better or not than treating only those who relapse and start treatment at relapse.”
According to Eggermont, the main limitation of the study is that we need more time before we can determine whether these positive recurrence-free survival results will lead to improvement in overall survival for the patients.
Eggermont AMM et al., abstract CT001: Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Efficacy and safety results from the EORTC 1325-MG/Keynote 053 double-blinded phase III trial
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